Skip to content
2000
image of Dynamin-related Protein 1 and the NLRP3 Inflammasome in Parkinson’s Disease: Mechanistic Insights and Therapeutic Opportunities

Abstract

Introduction

Parkinson’s disease (PD) is characterized by the progressive destruction of the dopaminergic cells in the substantia nigra region. The incidence of PD continues to rise, with over 8.5 million people affected in 2019 and projections indicating it could reach over 17 million by 2040 compared with levels observed since 1980. This review examines the mechanistic role of Dynamin-Related Protein 1 (Drp1) and Nod-Like Receptor Family Pyrin Domain-Containing 3 (NLRP3) inflammasome in the development and pathogenesis of PD.

Methods

The information was collected from databases such as PubMed, Embase, Google Scholar, Web of Science, and Elsevier database.

Results

There is a potential for Drp1 and NLRP3 pathways to serve as therapeutic targets in PD. Drp1 inhibitors, such as Mdivi-1, aid in mediating mitochondrial homeostasis, and NLRP3 inhibitors prevent inflammation. Natural compounds that modulate such pathways include resveratrol and curcumin, and preclinical models demonstrate multi-target neuroprotection via direct antioxidant and anti-inflammatory properties.

Discussion

The intricate relationship among oxidative stress, mitochondrial dynamics and inflammation indicates that a combination drug therapy approach is more likely to be effective compared to a single-agent strategy. In a subsequent phase, there is a need for improved formulation and enhancement of natural compounds to maximize their bioavailability and efficacy, particularly in terms of selective Drp1 and NLRP3 inhibitors.

Conclusion

The Drp1–NLRP3 axis is one of the essential mechanistic connections between mitochondrial dynamics and neuroinflammation in PD. Focusing on this axis could offer novel therapeutic options, and advancing these approaches could pave the way for therapies that not only alleviate symptoms but also slow or halt the progression of the disease.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmm/10.2174/0115665240397746250915001750
2025-09-26
2025-11-06

  • From This Site

    /content/journals/cmm/10.2174/0115665240397746250915001750
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Dorsey E.R. Bloem B.R. Parkinson’s disease is predominantly an environmental disease. J. Parkinsons Dis. 2024 14 3 451 465 10.3233/JPD‑230357 38217613
    [Google Scholar]
  2. Orozco J.L. Valderrama-Chaparro J.A. Pinilla-Monsalve G.D. Parkinson’s disease prevalence, age distribution and staging in Colombia. Neurol. Int. 2020 12 1 8401 10.4081/ni.2020.8401 32774822
    [Google Scholar]
  3. Goyal V. Radhakrishnan D.M. Parkinson’s disease: A review. Neurol. India 2018 66 7 26 (Suppl.) 10.4103/0028‑3886.226451 29503325
    [Google Scholar]
  4. Khan A.Z. Lavu D. Neal R.D. Parkinson’s disease: A scoping review of the quantitative and qualitative evidence of its diagnostic accuracy in primary care. Br. J. Gen. Pract. 2024 74 741 e227 e232 10.3399/BJGP.2023.0409 38164554
    [Google Scholar]
  5. Tenchov R. Sasso J.M. Zhou Q.A. Evolving landscape of parkinson’s disease research: Challenges and perspectives. ACS Omega 2025 10 2 1864 1892 10.1021/acsomega.4c09114 39866628
    [Google Scholar]
  6. Papagiouvannis G. Theodosis-Nobelos P. Rekka E.A. A review on therapeutic strategies against parkinson’s disease: Current trends and future perspectives. Mini Rev. Med. Chem. 2025 25 2 96 111 10.2174/0113895575303788240606054620 38918988
    [Google Scholar]
  7. Peggion C. Calì T. Brini M. Mitochondria dysfunction and neuroinflammation in neurodegeneration: Who comes first? Antioxidants 2024 13 2 240 10.3390/antiox13020240 38397838
    [Google Scholar]
  8. Sun F Fang M Zhang H Drp1: Focus on diseases triggered by the mitochondrial pathway cell biochem biophys 2024 82 2 435 55 10.1007/s12013‑024‑01245‑5 38438751
    [Google Scholar]
  9. Adebayo M. Singh S. Singh A.P. Dasgupta S. Mitochondrial fusion and fission: The fine‐tune balance for cellular homeostasis. FASEB J. 2021 35 6 e21620 10.1096/fj.202100067R 34048084
    [Google Scholar]
  10. Cicero J. Manor U. Beyond static snapshots: Mitochondria in action. Curr. Opin. Cell Biol. 2025 92 1 102460 10.1016/j.ceb.2024.102460 39736172
    [Google Scholar]
  11. Henrich M.T. Oertel W.H. Surmeier D.J. Geibl F.F. Mito-chondrial dysfunction in Parkinson’s disease – a key disease hallmark with therapeutic potential. Mol. Neurodegener. 2023 18 1 83 10.1186/s13024‑023‑00676‑7 37951933
    [Google Scholar]
  12. Grel H. Woznica D. Ratajczak K. Mitochondrial dynamics in neurodegenerative diseases: Unraveling the role of fusion and fission processes. Int. J. Mol. Sci. 2023 24 17 13033 10.3390/ijms241713033 37685840
    [Google Scholar]
  13. Chen S. Li Q. Shi H. Li F. Duan Y. Guo Q. New insights into the role of mitochondrial dynamics in oxidative stress-induced diseases. Biomed. Pharmacother. 2024 178 2 117084 10.1016/j.biopha.2024.117084 39088967
    [Google Scholar]
  14. Liu Y.J. McIntyre R.L. Janssens G.E. Houtkooper R.H. Mitochondrial fission and fusion: A dynamic role in aging and potential target for age-related disease. Mech. Ageing Dev. 2020 186 2 111212 10.1016/j.mad.2020.111212 32017944
    [Google Scholar]
  15. Ren J. Xiang B. Xueling L. Molecular mechanisms of mitochondrial homeostasis regulation in neurons and possible therapeutic approaches for Alzheimer’s disease. Heliyon 2024 10 17 e36470 10.1016/j.heliyon.2024.e36470 39281517
    [Google Scholar]
  16. Posey A.E. Ross K.A. Bagheri M. The variable domain from dynamin‐related protein 1 promotes liquid–liquid phase separation that enhances its interaction with cardiolipin‐containing membranes. Protein Sci. 2023 32 11 e4787 10.1002/pro.4787 37743569
    [Google Scholar]
  17. Rochon K. Bauer B.L. Roethler N.A. Structural basis for regulated assembly of the mitochondrial fission GTPase Drp1. Nat. Commun. 2024 15 1 1328 10.1038/s41467‑024‑45524‑4 38351080
    [Google Scholar]
  18. Nandan P.K. Job A.T. Ramasamy T. DRP1 association in inflammation and metastasis: A review. Curr. Drug Targets 2024 25 13 909 918 10.2174/0113894501304751240819111831 39248071
    [Google Scholar]
  19. Ford M.G.J. Chappie J.S. The structural biology of the dynamin‐related proteins: New insights into a diverse, multitalented family. Traffic 2019 20 10 717 740 10.1111/tra.12676 31298797
    [Google Scholar]
  20. Duan C. Liu R. Kuang L. Activated Drp1 initiates the formation of endoplasmic reticulum‐mitochondrial contacts via shrm4‐mediated actin bundling. Adv. Sci. 2023 10 36 2304885 10.1002/advs.202304885 37909346
    [Google Scholar]
  21. Mooli R.G.R. Mukhi D. Chen Z. Buckner N. Ramakrishnan S.K. An indispensable role for dynamin-related protein 1 in beige and brown adipogenesis. J. Cell Sci. 2020 133 18 jcs247593 10.1242/jcs.247593 32843579
    [Google Scholar]
  22. Zerihun M. Sukumaran S. Qvit N. The Drp1-mediated mitochondrial fission protein interactome as an emerging core player in mitochondrial dynamics and cardiovascular disease therapy. Int. J. Mol. Sci. 2023 24 6 5785 10.3390/ijms24065785 36982862
    [Google Scholar]
  23. Yu R. Liu T. Ning C. The phosphorylation status of Ser-637 in dynamin-related protein 1 (Drp1) does not determine Drp1 recruitment to mitochondria. J. Biol. Chem. 2019 294 46 17262 17277 10.1074/jbc.RA119.008202 31533986
    [Google Scholar]
  24. Cui Y. Zheng Z. Zhou Q. The role of clock control of DRP1 activity involved in postoperative cognitive dysfunction. Exp. Neurol. 2025 385 2 115140 10.1016/j.expneurol.2025.115140 39788309
    [Google Scholar]
  25. Song S.B. Park J.S. Jang S.Y. Hwang E.S. Nicotinamide treatment facilitates mitochondrial fission through Drp1 activation mediated by SIRT1-induced changes in cellular levels of cAMP and Ca2+. Cells 2021 10 3 612 10.3390/cells10030612 33802063
    [Google Scholar]
  26. Liu A. Hatch A.L. Higgs H.N. Effects of phosphorylation on Drp1 activation by its receptors, actin, and cardiolipin. Mol. Biol. Cell 2024 35 2 ar16 10.1091/mbc.E23‑11‑0427 38019609
    [Google Scholar]
  27. Yamada S. Sato A. Ishihara N. Akiyama H. Sakakibara S. Drp1 SUMO/deSUMOylation by Senp5 isoforms influences ER tubulation and mitochondrial dynamics to regulate brain development. iScience 2021 24 12 103484 10.1016/j.isci.2021.103484 34988397
    [Google Scholar]
  28. Lee D. Kim J.E. PDI-mediated S-nitrosylation of DRP1 facilitates DRP1-S616 phosphorylation and mitochondrial fission in CA1 neurons. Cell Death Dis. 2018 9 9 869 10.1038/s41419‑018‑0910‑5 30158524
    [Google Scholar]
  29. Mao Y. Liu K. Yang Y. Liang Y. Gong Z. Wu K. Hypoxia‐induced SENP3 promotes chemosensitivity and mitochondrial fission via deSUMOylation of Drp1. Head Neck 2024 46 11 2776 2788 10.1002/hed.27821 38769935
    [Google Scholar]
  30. Uoselis L. Nguyen T.N. Lazarou M. Mitochondrial degradation: Mitophagy and beyond. Mol. Cell 2023 83 19 3404 3420 10.1016/j.molcel.2023.08.021 37708893
    [Google Scholar]
  31. Shiiba I. Takeda K. Nagashima S. Yanagi S. Overview of mitochondrial E3 ubiquitin ligase MITOL/MARCH5 from molecular mechanisms to diseases. Int. J. Mol. Sci. 2020 21 11 3781 10.3390/ijms21113781 32471110
    [Google Scholar]
  32. Pedrera L. Prieto Clemente L. Dahlhaus A. Ferroptosis triggers mitochondrial fragmentation via Drp1 activation. Cell Death Dis. 2025 16 1 40 10.1038/s41419‑024‑07312‑2 39863602
    [Google Scholar]
  33. Oshima Y. Cartier E. Boyman L. Parkin-independent mitophagy via Drp1-mediated outer membrane severing and inner membrane ubiquitination. J. Cell Biol. 2021 220 6 e202006043 10.1083/jcb.202006043 33851959
    [Google Scholar]
  34. Bao F. Xiao J. Zhou L. Autophagy‐independent mitochondrial quality control: Mechanisms and disease associations. MedComm Future Med 2022 1 2 e25 10.1002/mef2.25
    [Google Scholar]
  35. Kornfeld O.S. Qvit N. Haileselassie B. Shamloo M. Bernardi P. Mochly-Rosen D. Interaction of mitochondrial fission factor with dynamin related protein 1 governs physiological mitochondrial function in vivo. Sci. Rep. 2018 8 1 14034 10.1038/s41598‑018‑32228‑1 30232469
    [Google Scholar]
  36. Shi W. Tan C. Liu C. Chen D. Mitochondrial fission mediated by Drp1-Fis1 pathway and neurodegenerative diseases. Rev. Neurosci. 2023 34 3 275 294 10.1515/revneuro‑2022‑0056 36059131
    [Google Scholar]
  37. Yang J. Chen P. Cao Y. Chemical inhibition of mitochondrial fission via targeting the DRP1-receptor interaction. Cell Chem. Biol. 2023 30 3 278 294.e11 10.1016/j.chembiol.2023.02.002 36827981
    [Google Scholar]
  38. Trinh D. Israwi A.R. Arathoon L.R. Gleave J.A. Nash J.E. The multi‐faceted role of mitochondria in the pathology of Parkinson’s disease. J. Neurochem. 2021 156 6 715 752 10.1111/jnc.15154 33616931
    [Google Scholar]
  39. Banerjee R. Mukherjee A. Nagotu S. Mitochondrial dynamics and its impact on human health and diseases: Inside the DRP1 blackbox. J. Mol. Med. (Berl.) 2022 100 1 1 21 10.1007/s00109‑021‑02150‑7 34657190
    [Google Scholar]
  40. Erekat N.S. Apoptosis and its therapeutic implications in neurodegenerative diseases. Clin. Anat. 2022 35 1 65 78 10.1002/ca.23792 34558138
    [Google Scholar]
  41. Dong-Chen X. Yong C. Yang X. Chen-Yu S. Li-Hua P. Signaling pathways in Parkinson’s disease: Molecular mechanisms and therapeutic interventions. Signal Transduct. Target. Ther. 2023 8 1 73 10.1038/s41392‑023‑01353‑3 36810524
    [Google Scholar]
  42. Jang J.E. Hwang D.Y. Eom J.I. DRP1 Inhibition Enhances venetoclax-induced mitochondrial apoptosis in TP53-mutated acute myeloid leukemia cells through BAX/BAK activation. Cancers 2023 15 3 745 10.3390/cancers15030745 36765703
    [Google Scholar]
  43. Jenner A. Peña-Blanco A. Salvador-Gallego R. DRP1 interacts directly with BAX to induce its activation and apoptosis. EMBO J. 2022 41 8 e108587 10.15252/embj.2021108587 35023587
    [Google Scholar]
  44. Liang H. Ma Z. Zhong W. Liu J. Sugimoto K. Chen H. Regulation of mitophagy and mitochondrial function: Natural compounds as potential therapeutic strategies for Parkinson’s disease. Phytother. Res. 2024 38 4 1838 1862 10.1002/ptr.8156 38356178
    [Google Scholar]
  45. Chen W. Chen X. Wang L. TIPE3 represses head and neck squamous cell carcinoma progression via triggering PGAM5 mediated mitochondria dysfunction. Cell Death Dis. 2023 14 4 251 10.1038/s41419‑023‑05775‑3 37024453
    [Google Scholar]
  46. Xie L. Shi F. Tan Z. Li Y. Bode A.M. Cao Y. Mitochondrial network structure homeostasis and cell death. Cancer Sci. 2018 109 12 3686 3694 10.1111/cas.13830 30312515
    [Google Scholar]
  47. Zhang S. Che L. He C. Drp1 and RB interaction to mediate mitochondria-dependent necroptosis induced by cadmium in hepatocytes. Cell Death Dis. 2019 10 7 523 10.1038/s41419‑019‑1730‑y 31285421
    [Google Scholar]
  48. Bock F.J. Tait S.W.G. Mitochondria as multifaceted regulators of cell death. Nat. Rev. Mol. Cell Biol. 2020 21 2 85 100 10.1038/s41580‑019‑0173‑8 31636403
    [Google Scholar]
  49. Villalpando-Rodriguez G.E. Gibson S.B. Reactive oxygen species (ROS) regulates different types of cell death by acting as a rheostat. Oxid. Med. Cell. Longev. 2021 2021 1 9912436 10.1155/2021/9912436 34426760
    [Google Scholar]
  50. Zhang Y. Deng Q. Hong H. Qian Z. Wan B. Xia M. Caffeic acid phenethyl ester inhibits neuro-inflammation and oxidative stress following spinal cord injury by mitigating mitochondrial dysfunction via the SIRT1/PGC1α/DRP1 signaling pathway. J. Transl. Med. 2024 22 1 304 10.1186/s12967‑024‑05089‑8 38528569
    [Google Scholar]
  51. Xu S. Li S. Bjorklund M. Xu S. Mitochondrial fragmentation and ROS signaling in wound response and repair. Cell Regen. 2022 11 1 38 10.1186/s13619‑022‑00141‑8 36451031
    [Google Scholar]
  52. Anzell A.R. Fogo G.M. Gurm Z. Mitochondrial fission and mitophagy are independent mechanisms regulating ischemia/reperfusion injury in primary neurons. Cell Death Dis. 2021 12 5 475 10.1038/s41419‑021‑03752‑2 33980811
    [Google Scholar]
  53. Sukhorukov V.S. Baranich T.I. Egorova A.V. Mitochondrial dynamics in brain cells during normal and pathological aging. Int. J. Mol. Sci. 2024 25 23 12855 10.3390/ijms252312855 39684566
    [Google Scholar]
  54. Favaro G. Romanello V. Varanita T. DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass. Nat. Commun. 2019 10 1 2576 10.1038/s41467‑019‑10226‑9 31189900
    [Google Scholar]
  55. Kamienieva I. Duszyński J. Szczepanowska J. Multitasking guardian of mitochondrial quality: Parkin function and Parkinson’s disease. Transl. Neurodegener. 2021 10 1 5 10.1186/s40035‑020‑00229‑8 33468256
    [Google Scholar]
  56. Kumar M. Acevedo-Cintrón J. Jhaldiyal A. Defects in mitochondrial biogenesis drive mitochondrial alterations in PARKIN-deficient human dopamine neurons. Stem Cell Reports 2020 15 3 629 645 10.1016/j.stemcr.2020.07.013 32795422
    [Google Scholar]
  57. Moradi Vastegani S. Nasrolahi A. Ghaderi S. Mitochondrial dysfunction and Parkinson’s disease: Patho-genesis and therapeutic strategies. Neurochem. Res. 2023 48 8 2285 2308 10.1007/s11064‑023‑03904‑0 36943668
    [Google Scholar]
  58. Fan J.J. Ding W.D. Liang Y.F. Diosgenin derivative ML5 attenuates MPTP-induced neuronal impairment via regulating AMPK/PGC-1α-mediated mitochondrial biogenesis and fusion/fission. Am. J. Transl. Res. 2024 16 8 3582 3598 10.62347/JBRE5043 39262707
    [Google Scholar]
  59. Li T. Zhang W. Kang X. Salidroside protects dopaminergic neurons by regulating the mitochondrial MEF2D‐ND6 pathway in the MPTP/MPP + ‐induced model of Parkinson’s disease. J. Neurochem. 2020 153 2 276 289 10.1111/jnc.14868 31520529
    [Google Scholar]
  60. Gu Y. Zhang J. Zhao X. Olfactory dysfunction and its related molecular mechanisms in Parkinson’s disease. Neural Regen. Res. 2024 19 3 583 590 10.4103/1673‑5374.380875 37721288
    [Google Scholar]
  61. Ruiz A. Quintela-López T. Sánchez-Gómez M.V. Gaminde-Blasco A. Alberdi E. Matute C. Mitochondrial division inhibitor 1 disrupts oligodendrocyte Ca 2+ homeostasis and mitochondrial function. Glia 2020 68 9 1743 1756 10.1002/glia.23802 32060978
    [Google Scholar]
  62. Su Z. Li C. Wang H. Zheng M. Chen Q. Inhibition of DRP1-dependent mitochondrial fission by Mdivi-1 alleviates atherosclerosis through the modulation of M1 polarization. J. Transl. Med. 2023 21 1 427 10.1186/s12967‑023‑04270‑9 37386574
    [Google Scholar]
  63. Rosdah A.A. Abbott B.M. Langendorf C.G. A novel small molecule inhibitor of human Drp1. Sci. Rep. 2022 12 1 21531 10.1038/s41598‑022‑25464‑z 36513726
    [Google Scholar]
  64. Pascucci B. Spadaro F. Pietraforte D. DRP1 Inhibition rescues mitochondrial integrity and excessive apoptosis in CS-A disease cell models. Int. J. Mol. Sci. 2021 22 13 7123 10.3390/ijms22137123 34281194
    [Google Scholar]
  65. Hu Z. Mao C. Wang H. CHIP protects against MPP+/MPTP-induced damage by regulating Drp1 in two models of Parkinson’s disease. Aging 2021 13 1 1458 1472 10.18632/aging.202389 33472166
    [Google Scholar]
  66. Chen C. McDonald D. Blain A. Parkinson’s disease neurons exhibit alterations in mitochondrial quality control proteins. NPJ Parkinsons Dis. 2023 9 1 120 10.1038/s41531‑023‑00564‑3 37553379
    [Google Scholar]
  67. Meng K. Jia H. Hou X. Mitochondrial Dysfunction in Neurodegenerative Diseases: Mechanisms and Corres-ponding Therapeutic Strategies. Biomedicines 2025 13 2 327 10.3390/biomedicines13020327 40002740
    [Google Scholar]
  68. Borsche M. Pereira S.L. Klein C. Grünewald A. Mitochondria and Parkinson’s disease: Clinical, molecular, and translational aspects. J. Parkinsons Dis. 2021 11 1 45 60 10.3233/JPD‑201981 33074190
    [Google Scholar]
  69. Sohrabi T. Mirzaei-Behbahani B. Zadali R. Pirhaghi M. Morozova-Roche L.A. Meratan A.A. Common mechanisms underlying α-synuclein-induced mitochondrial dysfunction in Parkinson’s disease. J. Mol. Biol. 2023 435 12 167992 10.1016/j.jmb.2023.167992 36736886
    [Google Scholar]
  70. Ganjam G.K. Bolte K. Matschke L.A. Mitochondrial damage by α-synuclein causes cell death in human dopaminergic neurons. Cell Death Dis. 2019 10 11 865 10.1038/s41419‑019‑2091‑2 31727879
    [Google Scholar]
  71. Portz P. Lee M.K. Changes in Drp1 function and mitochondrial morphology are associated with the α-synuclein pathology in a transgenic mouse model of Parkinson’s disease. Cells 2021 10 4 885 10.3390/cells10040885 33924585
    [Google Scholar]
  72. Ramachandran R. Schmid S.L. The dynamin superfamily. Curr. Biol. 2018 28 8 R411 R416 10.1016/j.cub.2017.12.013 29689225
    [Google Scholar]
  73. Singh S. Singh R.K. Recent advancements in the understanding of the alterations in mitochondrial biogenesis in Alzheimer’s disease. Mol. Biol. Rep. 2025 52 1 173 10.1007/s11033‑025‑10297‑6 39880979
    [Google Scholar]
  74. Oliver D. Reddy P. Dynamics of dynamin-related protein 1 in Alzheimer’s disease and other neurodegenerative diseases. Cells 2019 8 9 961 10.3390/cells8090961 31450774
    [Google Scholar]
  75. Jo M. Lee S. Kim K. Lee S. Kim S.R. Kim H.J. Inhibition of MEK5 suppresses TDP-43 toxicity via the mTOR-independent activation of the autophagy-lysosome pathway. Biochem. Biophys. Res. Commun. 2019 513 4 925 932 10.1016/j.bbrc.2019.04.088 31005259
    [Google Scholar]
  76. Qi Z. Huang Z. Xie F. Chen L. Dynamin‐related protein 1: A critical protein in the pathogenesis of neural system dysfunctions and neurodegenerative diseases. J. Cell. Physiol. 2019 234 7 10032 10046 10.1002/jcp.27866 30515821
    [Google Scholar]
  77. Geng J. Liu W. Gao J. Andrographolide alleviates Parkinsonism in MPTP‐PD mice via targeting mitochondrial fission mediated by dynamin‐related protein 1. Br. J. Pharmacol. 2019 176 23 4574 4591 10.1111/bph.14823 31389613
    [Google Scholar]
  78. Rios L. Pokhrel S. Li S.J. Heo G. Haileselassie B. Mochly-Rosen D. Targeting an allosteric site in dynamin-related protein 1 to inhibit Fis1-mediated mitochondrial dysfunction. Nat. Commun. 2023 14 1 4356 10.1038/s41467‑023‑40043‑0 37468472
    [Google Scholar]
  79. Wu D. Dasgupta A. Chen K.H. Identification of novel dynamin‐related protein 1 (Drp1) GTPase inhibitors: Therapeutic potential of Drpitor1 and Drpitor1a in cancer and cardiac ischemia‐reperfusion injury. FASEB J. 2020 34 1 1447 1464 10.1096/fj.201901467R 31914641
    [Google Scholar]
  80. Wu D. Jansen-van Vuuren R.D. Dasgupta A. Novel Drp1 GTPase inhibitor, drpitor1a: Efficacy in pulmonary hypertension. Hypertension 2024 81 10 2189 2201 10.1161/HYPERTENSIONAHA.124.22822 39162036
    [Google Scholar]
  81. Anis E. Zafeer M.F. Firdaus F. Ferulic acid reinstates mitochondrial dynamics through PGC1α expression modulation in 6‐hydroxydopamine lesioned rats. Phytother. Res. 2020 34 1 214 226 10.1002/ptr.6523 31657074
    [Google Scholar]
  82. Hedayatikatouli F. Kalyn M. Elsaid D. Mbesha H.A. Ekker M. Neuroprotective effects of ascorbic acid, vanillic acid, and ferulic acid in dopaminergic neurons of zebrafish. Biomedicines 2024 12 11 2497 10.3390/biomedicines12112497 39595063
    [Google Scholar]
  83. Mishra T. Nagarajan K. Dixit P.K. Kumar V. Neuroprotective potential of ferulic acid against cyclophosphamide‐induced neuroinflammation and behavioral changes. J. Food Biochem. 2022 46 12 e14436 10.1111/jfbc.14436 36166506
    [Google Scholar]
  84. Kwon S.H. Lee S.R. Park Y.J. Suppression of 6-hydroxydopamine-induced oxidative stress by hyperoside via activation of Nrf2/HO-1 signaling in dopaminergic neurons. Int. J. Mol. Sci. 2019 20 23 5832 10.3390/ijms20235832 31757050
    [Google Scholar]
  85. Di Giacomo S. Percaccio E. Gullì M. Recent advances in the neuroprotective properties of ferulic acid in Alzheimer’s disease: A narrative review. Nutrients 2022 14 18 3709 10.3390/nu14183709 36145084
    [Google Scholar]
  86. Xi Y. Feng D. Tao K. MitoQ protects dopaminergic neurons in a 6-OHDA induced PD model by enhancing Mfn2-dependent mitochondrial fusion via activation of PGC-1α. Biochim. Biophys. Acta Mol. Basis Dis. 2018 1864 9 2859 2870 10.1016/j.bbadis.2018.05.018 29842922
    [Google Scholar]
  87. Lin K.L. Lin K.J. Wang P.W. Resveratrol provides neuroprotective effects through modulation of mitochondrial dynamics and ERK1/2 regulated autophagy. Free Radic. Res. 2018 52 11-12 1371 1386 10.1080/10715762.2018.1489128 30693838
    [Google Scholar]
  88. Xu L. Hao L.P. Yu J. Curcumin protects against rotenone-induced Parkinson’s disease in mice by inhibiting microglial NLRP3 inflammasome activation and alleviating mitochondrial dysfunction. Heliyon 2023 9 5 e16195 10.1016/j.heliyon.2023.e16195 37234646
    [Google Scholar]
  89. Erazo-Oliveras A. Muñoz-Vega M. Salinas M.L. Wang X. Chapkin R.S. Dysregulation of cellular membrane homeostasis as a crucial modulator of cancer risk. FEBS J. 2024 291 7 1299 1352 10.1111/febs.16665 36282100
    [Google Scholar]
  90. Kamitsuka P.J. Ghanem M.M. Ziar R. McDonald S.E. Thomas M.G. Kwakye G.F. Defective mitochondrial dynamics and protein degradation pathways underlie cadmium-induced neurotoxicity and cell death in Huntington’s disease striatal cells. Int. J. Mol. Sci. 2023 24 8 7178 10.3390/ijms24087178 37108341
    [Google Scholar]
  91. Fakhri S. Kiani A. Jalili C. Intrathecal administration of melatonin ameliorates the neuroinflammation-mediated sensory and motor dysfunction in a rat model of compression spinal cord injury. Curr. Mol. Pharmacol. 2021 14 4 646 657 10.2174/1874467213666201230101811 33380311
    [Google Scholar]
  92. Goujon M. Liang Z. Soriano-Castell D. Currais A. Maher P. The neuroprotective flavonoids sterubin and fisetin maintain mitochondrial health under oxytotic/ferroptotic stress and improve bioenergetic efficiency in HT22 neuronal cells. Antioxidants 2024 13 4 460 10.3390/antiox13040460 38671908
    [Google Scholar]
  93. Sarkar C. Chaudhary P. Jamaddar S. Redox activity of flavonoids: Impact on human health, therapeutics, and chemical safety. Chem. Res. Toxicol. 2022 35 2 140 162 10.1021/acs.chemrestox.1c00348 35045245
    [Google Scholar]
  94. Pangou E. Bielska O. Guerber L. A PKD-MFF signaling axis couples mitochondrial fission to mitotic progression. Cell Rep. 2021 35 7 109129 10.1016/j.celrep.2021.109129 34010649
    [Google Scholar]
  95. Koch B. Traven A. Mdivi-1 and mitochondrial fission: Recent insights from fungal pathogens. Curr. Genet. 2019 65 4 837 845 10.1007/s00294‑019‑00942‑6 30783741
    [Google Scholar]
  96. Tábara L.C. Segawa M. Prudent J. Molecular mechanisms of mitochondrial dynamics. Nat. Rev. Mol. Cell Biol. 2025 26 2 123 146 10.1038/s41580‑024‑00785‑1 39420231
    [Google Scholar]
  97. Manczak M. Kandimalla R. Yin X. Reddy P.H. Mitochondrial division inhibitor 1 reduces dynamin-related protein 1 and mitochondrial fission activity. Hum. Mol. Genet. 2019 28 2 177 199 10.1093/hmg/ddy335 30239719
    [Google Scholar]
  98. Matsuishi Y.I. Kato H. Masuda K. Accelerated dentinogenesis by inhibiting the mitochondrial fission factor, dynamin related protein 1. Biochem. Biophys. Res. Commun. 2018 495 2 1655 1660 10.1016/j.bbrc.2017.12.026 29223396
    [Google Scholar]
  99. Jewell S. Herath A.M. Gordon R. Inflammasome activation in Parkinson’s disease. J. Parkinsons Dis. 2022 12 s1 S113 S128 10.3233/JPD‑223338 35848038
    [Google Scholar]
  100. Weber A.N.R. Bittner Z.A. Shankar S. Recent insights into the regulatory networks of NLRP3 inflammasome activation. J. Cell Sci. 2020 133 23 jcs248344 10.1242/jcs.248344 33273068
    [Google Scholar]
  101. Soraci L. Gambuzza M.E. Biscetti L. Toll-like receptors and NLRP3 inflammasome-dependent pathways in Parkinson’s disease: Mechanisms and therapeutic implications. J. Neurol. 2023 270 3 1346 1360 10.1007/s00415‑022‑11491‑3 36460875
    [Google Scholar]
  102. Kelley N. Jeltema D. Duan Y. He Y. The NLRP3 inflammasome: An overview of mechanisms of activation and regulation. Int. J. Mol. Sci. 2019 20 13 3328 10.3390/ijms20133328 31284572
    [Google Scholar]
  103. Sun Y. Liu K. Mechanistic insights into influenza A virus-induced cell death and emerging treatment strategies. Vet. Sci. 2024 11 11 555 10.3390/vetsci11110555 39591329
    [Google Scholar]
  104. Gora I.M. Ciechanowska A. Ladyzynski P. NLRP3 inflammasome at the interface of inflammation, endothelial dysfunction, and type 2 diabetes. Cells 2021 10 2 314 10.3390/cells10020314 33546399
    [Google Scholar]
  105. kodi T, Sankhe R, Gopinathan A, Nandakumar K, Kishore A. New insights on NLRP3 inflammasome: Mechanisms of activation, inhibition, and epigenetic regulation. J. Neuroimmune Pharmacol. 2024 19 1 7 10.1007/s11481‑024‑10101‑5 38421496
    [Google Scholar]
  106. Ising C. Venegas C. Zhang S. NLRP3 inflammasome activation drives tau pathology. Nature 2019 575 7784 669 673 10.1038/s41586‑019‑1769‑z 31748742
    [Google Scholar]
  107. Ilari S. Giancotti L.A. Lauro F. Natural antioxidant control of neuropathic pain—exploring the role of mitochondrial sirt3 pathway. Antioxidants 2020 9 11 1103 10.3390/antiox9111103 33182469
    [Google Scholar]
  108. Alikatte K. Palle S. Rajendra Kumar J. Pathakala N. Fisetin improved rotenone-induced behavioral deficits, oxidative changes, and mitochondrial dysfunctions in rat model of Parkinson’s disease. J. Diet. Suppl. 2021 18 1 57 71 10.1080/19390211.2019.1710646 31992104
    [Google Scholar]
  109. Hao S. Huang H. Ma R.Y. Zeng X. Duan C.Y. Multifaceted functions of Drp1 in hypoxia/ischemia-induced mitochondrial quality imbalance: From regulatory mechanism to targeted therapeutic strategy. Mil. Med. Res. 2023 10 1 46 10.1186/s40779‑023‑00482‑8 37833768
    [Google Scholar]
  110. Babamale A.O. Chen S.T. Nod-like receptors: Critical intracellular sensors for host protection and cell death in microbial and parasitic infections. Int. J. Mol. Sci. 2021 22 21 11398 10.3390/ijms222111398 34768828
    [Google Scholar]
  111. Riaz M. Rehman A.U. Shah S.A. Predicting multi-interfacial binding mechanisms of NLRP3 and ASC pyrin domains in inflammasome activation. ACS Chem. Neurosci. 2021 12 4 603 612 10.1021/acschemneuro.0c00519 33504150
    [Google Scholar]
  112. Spel L. Hou C. Theodoropoulou K. HSP90β controls NLRP3 autoactivation. Sci. Adv. 2024 10 9 eadj6289 10.1126/sciadv.adj6289 38416826
    [Google Scholar]
  113. Coll R.C. Hill J.R. Day C.J. MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition. Nat. Chem. Biol. 2019 15 6 556 559 10.1038/s41589‑019‑0277‑7 31086327
    [Google Scholar]
  114. Fu J. Wu H. Structural mechanisms of NLRP3 inflammasome assembly and activation. Annu. Rev. Immunol. 2023 41 1 301 316 10.1146/annurev‑immunol‑081022‑021207 36750315
    [Google Scholar]
  115. Sharif H. Wang L. Wang W.L. Structural mechanism for NEK7-licensed activation of NLRP3 inflammasome. Nature 2019 570 7761 338 343 10.1038/s41586‑019‑1295‑z 31189953
    [Google Scholar]
  116. Li Y. Fu T.M. Lu A. Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1. Proc. Natl. Acad. Sci. USA 2018 115 43 10845 10852 10.1073/pnas.1810524115 30279182
    [Google Scholar]
  117. Pellegrini E. Desfosses A. Wallmann A. RIP2 filament formation is required for NOD2 dependent NF-κB signalling. Nat. Commun. 2018 9 1 4043 10.1038/s41467‑018‑06451‑3 30279485
    [Google Scholar]
  118. Swanson K.V. Deng M. Ting J.P.Y. The NLRP3 inflamma-some: Molecular activation and regulation to therapeutics. Nat. Rev. Immunol. 2019 19 8 477 489 10.1038/s41577‑019‑0165‑0 31036962
    [Google Scholar]
  119. Sho T. Xu J. Role and mechanism of ROS scavengers in alleviating NLRP3‐mediated inflammation. Biotechnol. Appl. Biochem. 2019 66 1 4 13 10.1002/bab.1700 30315709
    [Google Scholar]
  120. Zheng M. Williams E.P. Malireddi R.K.S. Impaired NLRP3 inflammasome activation/pyroptosis leads to robust inflammatory cell death via caspase-8/RIPK3 during coronavirus infection. J. Biol. Chem. 2020 295 41 14040 14052 10.1074/jbc.RA120.015036 32763970
    [Google Scholar]
  121. Schwarzer R. Jiao H. Wachsmuth L. Tresch A. Pasparakis M. FADD and caspase-8 regulate gut homeostasis and inflammation by controlling MLKL-and GSDMD-mediated death of intestinal epithelial cells. Immunity 2020 52 6 978 993.e6 10.1016/j.immuni.2020.04.002 32362323
    [Google Scholar]
  122. Jiang M. Qi L. Li L. Wu Y. Song D. Li Y. Caspase‐8: A key protein of cross‐talk signal way in “ PANoptosis ” in cancer. Int. J. Cancer 2021 149 7 1408 1420 10.1002/ijc.33698 34028029
    [Google Scholar]
  123. Maalim A.A. Wang Z. Huang Y. Lei T. RACK1 Promotes Meningioma Progression by Activation of NF-κB Pathway via Preventing CSNK2B from Ubiquitination Degradation. Cancers 2024 16 4 767 10.3390/cancers16040767 38398158
    [Google Scholar]
  124. Akther M. Haque M.E. Park J. Kang T.B. Lee K.H. NLRP3 ubiquitination—a new approach to target NLRP3 inflammasome activation. Int. J. Mol. Sci. 2021 22 16 8780 10.3390/ijms22168780 34445484
    [Google Scholar]
  125. Zhong Z. Liang S. Sanchez-Lopez E. New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature 2018 560 7717 198 203 10.1038/s41586‑018‑0372‑z 30046112
    [Google Scholar]
  126. Nie L. Fei C. Fan Y. Consecutive palmitoylation and phosphorylation orchestrates NLRP3 membrane trafficking and inflammasome activation. Mol. Cell 2024 84 17 3336 3353.e7 10.1016/j.molcel.2024.08.001 39173637
    [Google Scholar]
  127. Fang R. Cheng Y. Chen P. Hu J. Yang L. PGC-1α agonist ZLN005 ameliorates OVA-induced asthma in BALB/c mice through modulating the NF-κB-p65/NLRP3 pathway. Iran. J. Basic Med. Sci. 2025 28 6 710 717 10.22038/ijbms.2025.83166.17982 40343297
    [Google Scholar]
  128. Xu J. Núñez G. The NLRP3 inflammasome: Activation and regulation. Trends Biochem. Sci. 2023 48 4 331 344 10.1016/j.tibs.2022.10.002 36336552
    [Google Scholar]
  129. Kanno Y. The Roles of Fibrinolytic Factors in Bone Destruction Caused by Inflammation. Cells 2024 13 6 516 10.3390/cells13060516 38534360
    [Google Scholar]
  130. Putnam C.D. Broderick L. Hoffman H.M. The discovery of NLRP3 and its function in cryopyrin‐associated periodic syndromes and innate immunity. Immunol. Rev. 2024 322 1 259 282 10.1111/imr.13292 38146057
    [Google Scholar]
  131. Moretti J. Jia B. Hutchins Z. Caspase-11 interaction with NLRP3 potentiates the noncanonical activation of the NLRP3 inflammasome. Nat. Immunol. 2022 23 5 705 717 10.1038/s41590‑022‑01192‑4 35487985
    [Google Scholar]
  132. Xu J. Zhang L. Duan Y. NEK7 phosphorylation amplifies NLRP3 inflammasome activation downstream of potassium efflux and gasdermin D. Sci. Immunol. 2025 10 103 eadl2993 10.1126/sciimmunol.adl2993 39752537
    [Google Scholar]
  133. Matico R. Grauwen K. Chauhan D. Navigating from cellular phenotypic screen to clinical candidate: Selective targeting of the NLRP3 inflammasome. EMBO Mol. Med. 2024 17 1 54 84 10.1038/s44321‑024‑00181‑4 39653810
    [Google Scholar]
  134. Shi Y. He T. Liu H. Ganglioside GA2-mediated caspase-11 activation drives macrophage pyroptosis aggravating intimal hyperplasia after arterial injury. Int. J. Biol. Sci. 2025 21 1 433 453 10.7150/ijbs.97106 39744431
    [Google Scholar]
  135. Senkevich K. Liu L. Alvarado C.X. Leonard H.L. Nalls M.A. Gan-Or Z. Lack of genetic evidence for NLRP3 inflammasome involvement in Parkinson’s disease pathogenesis. NPJ Parkinsons Dis. 2024 10 1 145 10.1038/s41531‑024‑00744‑9 39103393
    [Google Scholar]
  136. Gupta S. Cassel S.L. Sutterwala F.S. Dagvadorj J. Regulation of the NLRP3 inflammasome by autophagy and mitophagy. Immunol. Rev. 2025 329 1 e13410 10.1111/imr.13410 39417249
    [Google Scholar]
  137. Dong H. Zhao B. Chen J. Mitochondrial calcium uniporter promotes phagocytosis-dependent activation of the NLRP3 inflammasome. Proc. Natl. Acad. Sci. USA 2022 119 26 e2123247119 10.1073/pnas.2123247119 35733245
    [Google Scholar]
  138. Rozario P. Pinilla M. Gorse L. Mechanistic basis for potassium efflux–driven activation of the human NLRP1 inflammasome. Proc. Natl. Acad. Sci. USA 2024 121 2 e2309579121 10.1073/pnas.2309579121 38175865
    [Google Scholar]
  139. Koumangoye R. The role of Cl − and K + efflux in NLRP3 inflammasome and innate immune response activation. Am. J. Physiol. Cell Physiol. 2022 322 4 C645 C652 10.1152/ajpcell.00421.2021 35171697
    [Google Scholar]
  140. Ren W. Rubini P. Tang Y. Engel T. Illes P. Inherent P2X7 receptors regulate macrophage functions during inflammatory diseases. Int. J. Mol. Sci. 2021 23 1 232 10.3390/ijms23010232 35008658
    [Google Scholar]
  141. Green J.P. Yu S. Martín-Sánchez F. Chloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome priming. Proc. Natl. Acad. Sci. USA 2018 115 40 E9371 E9380 10.1073/pnas.1812744115 30232264
    [Google Scholar]
  142. Zangiabadi S. Abdul-Sater A.A. Regulation of the NLRP3 inflammasome by posttranslational modifications. J. Immunol. 2022 208 2 286 292 10.4049/jimmunol.2100734 35017218
    [Google Scholar]
  143. B Gowda S Gowda D Kain V Sphingosine-1-phosphate interactions in the spleen and heart reflect extent of cardiac repair in mice and failing human hearts. Am. J. Physiol. Heart Circ. Physiol. 2021 321 3 H599 H611 10.1152/ajpheart.00314.2021 34415189
    [Google Scholar]
  144. Han L. Tieliwaerdi N. Li X. METTL3-deficiency m6A-dependently degrades MALAT1 to suppress NLRP3-mediated pyroptotic cell death and inflammation in Mycobacterium tuberculosis (H37Ra strain)-infected mouse macrophages. Tuberculosis (Edinb.) 2024 146 102502 10.1016/j.tube.2024.102502 38458103
    [Google Scholar]
  145. Gu P. Hui X. Zheng Q. Mitochondrial uncoupling protein 1 antagonizes atherosclerosis by blocking NLRP3 inflammasome–dependent interleukin-1β production. Sci. Adv. 2021 7 50 eabl4024 10.1126/sciadv.abl4024 34878840
    [Google Scholar]
  146. Xu H. Yu W. Sun S. Li C. Ren J. Zhang Y. TAX1BP1 protects against myocardial infarction-associated cardiac anomalies through inhibition of inflammasomes in a RNF34/MAVS/NLRP3-dependent manner. Sci. Bull. (Beijing) 2021 66 16 1669 1683 10.1016/j.scib.2021.01.030 36654301
    [Google Scholar]
  147. Zhang X. Zheng Y. Wang Z. Calpain: The regulatory point of cardiovascular and cerebrovascular diseases. Biomed. Pharmacother. 2024 179 117272 10.1016/j.biopha.2024.117272 39153432
    [Google Scholar]
  148. Billingham L.K. Stoolman J.S. Vasan K. Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation. Nat. Immunol. 2022 23 5 692 704 10.1038/s41590‑022‑01185‑3 35484407
    [Google Scholar]
  149. Wu Z. Bezwada D. Cai F. Electron transport chain inhibition increases cellular dependence on purine transport and salvage. Cell Metab. 2024 36 7 1504 1520.e9 10.1016/j.cmet.2024.05.014 38876105
    [Google Scholar]
  150. Ma Q. Lim C.S. Molecular Activation of NLRP3 Inflammasome by Particles and Crystals: A Continuing Challenge of Immunology and Toxicology. Annu. Rev. Pharmacol. Toxicol. 2024 64 1 417 433 10.1146/annurev‑pharmtox‑031023‑125300 37708431
    [Google Scholar]
  151. Paik S. Kim J.K. Silwal P. Sasakawa C. Jo E.K. An update on the regulatory mechanisms of NLRP3 inflammasome activation. Cell. Mol. Immunol. 2021 18 5 1141 1160 10.1038/s41423‑021‑00670‑3 33850310
    [Google Scholar]
  152. Subczynski W.K. Pasenkiewicz-Gierula M. Hypothetical pathway for formation of cholesterol microcrystals initiating the atherosclerotic process. Cell Biochem. Biophys. 2020 78 3 241 247 10.1007/s12013‑020‑00925‑2 32602057
    [Google Scholar]
  153. Boccia T. Pan W. Fattori V. Adjuvant conditioning shapes the adaptive immune response promoting immunotolerance via NLRP3/interleukin-1. iScience 2025 28 6 112653 10.1016/j.isci.2025.112653 40530419
    [Google Scholar]
  154. Gong T. Yang Y. Jin T. Jiang W. Zhou R. Orchestration of NLRP3 inflammasome activation by ion fluxes. Trends Immunol. 2018 39 5 393 406 10.1016/j.it.2018.01.009 29452983
    [Google Scholar]
  155. Inoue E. Minatozaki S. Shimizu S. Human β-Defensin 3 Inhibition of P. gingivalis LPS-Induced IL-1β Production by BV-2 Microglia through Suppression of Cathepsins B and L. Cells 2024 13 3 283 10.3390/cells13030283 38334675
    [Google Scholar]
  156. Eichholz K. Tran T.H. Chéneau C. Adenovirus-α-Defensin complexes induce NLRP3-associated maturation of human phagocytes via toll-like receptor 4 engagement. J. Virol. 2022 96 6 e01850 e21 10.1128/jvi.01850‑21 35080426
    [Google Scholar]
  157. Agnew A. Nulty C. Creagh E.M. Regulation, activation, and function of caspase-11 during health and disease. Int. J. Mol. Sci. 2021 22 4 1506 10.3390/ijms22041506 33546173
    [Google Scholar]
  158. Yi Y.S. Regulatory roles of the caspase-11 non-canonical inflammasome in inflammatory diseases. Immune Netw. 2018 18 6 e41 10.4110/in.2018.18.e41 30619627
    [Google Scholar]
  159. Rafeld H.L. Kolanus W. van Driel I.R. Hartland E.L. Interferon-induced GTPases orchestrate host cell-autonomous defence against bacterial pathogens. Biochem. Soc. Trans. 2021 49 3 1287 1297 10.1042/BST20200900 34003245
    [Google Scholar]
  160. Oh C. Spears T.J. Aachoui Y. Inflammasome‐mediated pyroptosis in defense against pathogenic bacteria. Immunol. Rev. 2025 329 1 e13408 10.1111/imr.13408 39404258
    [Google Scholar]
  161. Sugisawa R. Shanahan K.A. Davis G.M. Davey G.P. Bowie A.G. SARM1 regulates pro-inflammatory cytokine expression in human monocytes by NADase-dependent and -independent mechanisms. iScience 2024 27 6 109940 10.1016/j.isci.2024.109940 38832024
    [Google Scholar]
  162. Acuña-Castillo C. Escobar A. García-Gómez M. P2X7 Receptor in dendritic cells and macrophages: Implications in antigen presentation and t lymphocyte activation. Int. J. Mol. Sci. 2024 25 5 2495 10.3390/ijms25052495 38473744
    [Google Scholar]
  163. Huang Q. Qin D. Chen C. SHANK2-AS3: A potential biomarker for Parkinson’s disease and its role in neuronal apoptosis via NF-κB signaling in SH-SY5Y cells. Heliyon 2024 10 21 e38822 10.1016/j.heliyon.2024.e38822 39553632
    [Google Scholar]
  164. Molina-López C. Hurtado-Navarro L. García C.J. Pathogenic NLRP3 mutants form constitutively active inflammasomes resulting in immune-metabolic limitation of IL-1β production. Nat. Commun. 2024 15 1 1096 10.1038/s41467‑024‑44990‑0 38321014
    [Google Scholar]
  165. Yi Y.S. Functional interplay between non-canonical inflammasomes and autophagy in inflammatory responses and diseases. Korean J. Physiol. Pharmacol. 2025 29 2 129 138 10.4196/kjpp.24.240 39539180
    [Google Scholar]
  166. Sadeghdoust M. Das A. Kaushik D.K. Fueling neurodegeneration: Metabolic insights into microglia functions. J. Neuroinflammation 2024 21 1 300 10.1186/s12974‑024‑03296‑0 39551788
    [Google Scholar]
  167. Luo B. Li L. Song X.D. MicroRNA-7 attenuates secondary brain injury following experimental intracerebral hemorrhage via inhibition of NLRP3. J. Stroke Cerebrovasc. Dis. 2024 33 5 107670 10.1016/j.jstrokecerebrovasdis.2024.107670 38438086
    [Google Scholar]
  168. Yu J. Zhao Z. Li Y. Chen J. Huang N. Luo Y. Role of NLRP3 in Parkinson’s disease: Specific activation especially in dopaminergic neurons. Heliyon 2024 10 7 e28838 10.1016/j.heliyon.2024.e28838 38596076
    [Google Scholar]
  169. Wang B. Ma Y. Li S. GSDMD in peripheral myeloid cells regulates microglial immune training and neuroinflammation in Parkinson’s disease. Acta Pharm. Sin. B 2023 13 6 2663 2679 10.1016/j.apsb.2023.04.008 37425058
    [Google Scholar]
  170. Li L. Xu T. Qi X. Balanced regulation of ROS production and inflammasome activation in preventing early development of colorectal cancer. Immunol. Rev. 2025 329 1 e13417 10.1111/imr.13417 39523732
    [Google Scholar]
  171. Maharana J. Panda D. De S. Deciphering the ATP-binding mechanism(s) in NLRP-NACHT 3D models using structural bioinformatics approaches. PLoS One 2018 13 12 e0209420 10.1371/journal.pone.0209420 30571723
    [Google Scholar]
  172. Panicker N. Kam T.I. Wang H. Neuronal NLRP3 is a parkin substrate that drives neurodegeneration in Parkinson’s disease. Neuron 2022 110 15 2422 2437.e9 10.1016/j.neuron.2022.05.009 35654037
    [Google Scholar]
  173. Sánchez-Rodríguez R. Munari F. Angioni R. Targeting monoamine oxidase to dampen NLRP3 inflammasome activation in inflammation. Cell. Mol. Immunol. 2021 18 5 1311 1313 10.1038/s41423‑020‑0441‑8 32346102
    [Google Scholar]
  174. Çiftçi K.B. Erbakan K. Demirezen A. Erbaş O. Regulation, Activation, and Function of Caspase-11 in Inflammation. Journal of Experimental and Basic Medical Sciences 2022 3 2 179 184 10.5606/jebms.2022.1025
    [Google Scholar]
  175. Sharma B. Satija G. Madan A. Role of NLRP3 inflammasome and its inhibitors as emerging therapeutic drug candidate for Alzheimer’s disease: A review of mechanism of activation, regulation, and inhibition. Inflammation 2023 46 1 56 87 10.1007/s10753‑022‑01730‑0 36006570
    [Google Scholar]
  176. Ou Z. Zhou Y. Wang L. NLRP3 inflammasome inhibition prevents α-synuclein pathology by relieving autophagy dysfunction in chronic MPTP–treated nlrp3 knockout mice. Mol. Neurobiol. 2021 58 4 1303 1311 10.1007/s12035‑020‑02198‑5 33169332
    [Google Scholar]
  177. Tian Y-Y. Zhang Y-D. Gao Q. Angiotensin-(1–7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson’s disease. Neural Regen. Res. 2022 17 5 1138 1145 10.4103/1673‑5374.324854 34558543
    [Google Scholar]
  178. Zhu B. Yin D. Zhao H. Zhang L. The immunology of parkinson’s disease. Semin. Immunopathol. 2022 44 5 659 672 10.1007/s00281‑022‑00947‑3
    [Google Scholar]
  179. Ouerdane Y. Hassaballah M.Y. Nagah A. Exosomes in parkinson: Revisiting their pathologic role and potential applications. Pharmaceuticals 2022 15 1 76 10.3390/ph15010076
    [Google Scholar]
  180. Vasquez V. Kodavati M. Mitra J. Mitochondria-targeted oligomeric α-synuclein induces TOM40 degradation and mitochondrial dysfunction in Parkinson’s disease and parkinsonism-dementia of Guam. Cell Death Dis. 2024 15 12 914 10.1038/s41419‑024‑07258‑5 39695091
    [Google Scholar]
  181. Cheng J. Liao Y. Dong Y. Microglial autophagy defect causes parkinson disease-like symptoms by accelerating inflammasome activation in mice. Autophagy 2020 16 12 2193 2205 10.1080/15548627.2020.1719723 32003282
    [Google Scholar]
  182. Chakrabarti S. Bisaglia M. Oxidative stress and neuroinflammation in Parkinson’s disease: The role of dopamine oxidation products. Antioxidants 2023 12 4 955 10.3390/antiox12040955 37107329
    [Google Scholar]
  183. Nguyen L.T.N. Nguyen H.D. Kim Y.J. Role of NLRP3 inflammasome in Parkinson’s disease and therapeutic considerations. J. Parkinsons Dis. 2022 12 7 2117 2133 10.3233/JPD‑223290 35988226
    [Google Scholar]
  184. Jiang Y. He L. Green J. Discovery of second-generation NLRP3 inflammasome inhibitors: Design, synthesis, and biological characterization. J. Med. Chem. 2019 62 21 9718 9731 10.1021/acs.jmedchem.9b01155 31626545
    [Google Scholar]
  185. Ahmed S. Panda S.R. Kwatra M. Sahu B.D. Naidu V.G.M. Perillyl alcohol attenuates NLRP3 inflammasome activation and rescues dopaminergic neurons in experimental in vitro and in vivo models of Parkinson’s disease. ACS Chem. Neurosci. 2022 13 1 53 68 10.1021/acschemneuro.1c00550 34904823
    [Google Scholar]
  186. Levine P.M. Galesic A. Balana A.T. α-Synuclein O-GlcNAcylation alters aggregation and toxicity, revealing certain residues as potential inhibitors of Parkinson’s disease. Proc. Natl. Acad. Sci. USA 2019 116 5 1511 1519 10.1073/pnas.1808845116 30651314
    [Google Scholar]
  187. Tao Y. Sun Y. Lv S. Heparin induces α-synuclein to form new fibril polymorphs with attenuated neuropathology. Nat. Commun. 2022 13 1 4226 10.1038/s41467‑022‑31790‑7 35869048
    [Google Scholar]
  188. Vidya M.K. Kumar V.G. Sejian V. Bagath M. Krishnan G. Bhatta R. Toll-like receptors: Significance, ligands, signaling pathways, and functions in mammals. Int. Rev. Immunol. 2018 37 1 20 36 10.1080/08830185.2017.1380200 29028369
    [Google Scholar]
  189. Mohammadipour A. A focus on natural products for preventing and cure of mitochondrial dysfunction in Parkinson’s disease. Metab. Brain Dis. 2022 37 4 889 900 10.1007/s11011‑022‑00931‑8 35156154
    [Google Scholar]
  190. Liu Y. Qi X. Zhao Z. TIPE1‐mediated autophagy suppression promotes nasopharyngeal carcinoma cell proliferation via the AMPK/mTOR signalling pathway. J. Cell. Mol. Med. 2020 24 16 9135 9144 10.1111/jcmm.15550 32588529
    [Google Scholar]
  191. Chen J.A. Gene co-expression network analysis implicates microRNA processing in Parkinson’s disease pathogenesis. Neurodegener. Dis. 2018 18 4 191 199 10.1159/000490427 30089309
    [Google Scholar]
  192. Zhou X.G. Qiu W.Q. Yu L. Targeting microglial autophagic degradation of the NLRP3 inflammasome for identification of thonningianin A in Alzheimer’s disease. Inflamm. Regen. 2022 42 1 25 10.1186/s41232‑022‑00209‑7 35918778
    [Google Scholar]
  193. Vuu Y.M. Kadar Shahib A. Rastegar M. The potential therapeutic application of simvastatin for brain complications and mechanisms of action. Pharmaceuticals 2023 16 7 914 10.3390/ph16070914 37513826
    [Google Scholar]
  194. Alrouji M. Al-kuraishy H.M. Al-Gareeb A.I. Cyclin‐dependent kinase 5 (CDK5) inhibitors in Parkinson disease. J. Cell. Mol. Med. 2024 28 11 e18412 10.1111/jcmm.18412 38842132
    [Google Scholar]
  195. Qin Y. Zhao W. Posttranslational modifications of NLRP3 and their regulatory roles in inflammasome activation. Eur. J. Immunol. 2023 53 10 2350382 10.1002/eji.202350382 37382218
    [Google Scholar]
  196. Pergel E. Veres I. Csigi G.I. Czirják G. Translocation of TMEM175 lysosomal potassium channel to the plasma membrane by dynasore compounds. Int. J. Mol. Sci. 2021 22 19 10515 10.3390/ijms221910515 34638858
    [Google Scholar]
  197. Kosowski M. Smolarczyk-Kosowska J. Hachuła M. The effects of statins on neurotransmission and their neuroprotective role in neurological and psychiatric disorders. Molecules 2021 26 10 2838 10.3390/molecules26102838 34064670
    [Google Scholar]
  198. Allnutt A.B. Waters A.K. Kesari S. Yenugonda V.M. Physiological and pathological roles of Cdk5: Potential directions for therapeutic targeting in neurodegenerative disease. ACS Chem. Neurosci. 2020 11 9 1218 1230 10.1021/acschemneuro.0c00096 32286796
    [Google Scholar]
  199. Yoon C.S. Natural Products in the Treatment of Neuroinflammation at Microglia: Recent Trend and Features. Cells 2025 14 8 571 10.3390/cells14080571 40277896
    [Google Scholar]
  200. Malatt C. Maghzi H. Hogg E. Tan E. Khatiwala I. Tagliati M. Adrenergic blockers, statins, and non-steroidal anti-inflammatory drugs are associated with later age at onset in Parkinson’s disease. J. Neurol. 2025 272 3 255 10.1007/s00415‑025‑12989‑2 40047945
    [Google Scholar]
  201. Han Y.H. Liu X.D. Jin M.H. Sun H.N. Kwon T. Role of NLRP3 inflammasome-mediated neuronal pyroptosis and neuroinflammation in neurodegenerative diseases. Inflamm. Res. 2023 72 9 1839 1859 10.1007/s00011‑023‑01790‑4 37725102
    [Google Scholar]
  202. Fracassi A. Marangoni M. Rosso P. Statins, and the brain: More than lipid lowering agents? Curr. Neuropharmacol. 2018 17 1 59 83 10.2174/1570159X15666170703101816 28676012
    [Google Scholar]
  203. Bagheri H. Ghasemi F. Barreto G.E. Sathyapalan T. Jamialahmadi T. Sahebkar A. The effects of statins on microglial cells to protect against neurodegenerative disorders: A mechanistic review. Biofactors 2020 46 3 309 325 10.1002/biof.1597 31846136
    [Google Scholar]
  204. Boxberger N. Hecker M. Zettl U.K. Dysregulation of inflammasome priming and activation by MicroRNAs in human immune-mediated diseases. J. Immunol. 2019 202 8 2177 2187 10.4049/jimmunol.1801416 30962309
    [Google Scholar]
  205. Liu K. Guo L. Chen X. Liu L. Gao C. Microbial synthesis of glycosaminoglycans and their oligosaccharides. Trends Microbiol. 2023 31 4 369 383 10.1016/j.tim.2022.11.003 36517300
    [Google Scholar]
  206. Tu H.Y. Yuan B.S. Hou X.O. α‐synuclein suppresses microglial autophagy and promotes neurodegeneration in a mouse model of Parkinson’s disease. Aging Cell 2021 20 12 e13522 10.1111/acel.13522 34811872
    [Google Scholar]
  207. Gordon R. Albornoz E.A. Christie D.C. Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice. Sci. Transl. Med. 2018 10 465 eaah4066 10.1126/scitranslmed.aah4066 30381407
    [Google Scholar]
/content/journals/cmm/10.2174/0115665240397746250915001750
Loading
Dynamin-related Protein 1 and the NLRP3 Inflammasome in Parkinson’s Disease: Mechanistic Insights and Therapeutic Opportunities
Bentham Science Publishers ; https://doi.org/10.2174/0115665240397746250915001750
/content/journals/cmm/10.2174/0115665240397746250915001750
/content/journals/cmm/10.2174/0115665240397746250915001750
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: NLRP3 ; Parkinson’s disease ; neuroinflammation ; mitochondrial dynamics ; oxidative stress ; Drp1

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test